The proposed update of the Canadian Fluoroscopy Cohort Study (CFCS) will address critical gaps in knowledge of the long-term health risks of protracted radiation exposures from diagnostic imaging procedures. The rise of computerized X-ray tomography (CT) is remarkable with well over 85 million examinations per year performed in the United States alone. The causal association between high doses of gamma radiation and increased risks of cancer are firmly established, but the risks of low-dose X-ray radiation exposures protracted over a period of time remain undetermined. Current radiation safety standards for CT scans are based in large part on the study of Japanese atomic bomb (A-bomb) survivors exposed in 1945 to instantaneous high- energy gamma radiation. National and international radiation protection agencies recommend reducing estimates of excess risks from CT scans projected from the A-bomb data by a factor of 1.5-2.0, although recent studies of occupationally exposed workers show similar risks per unit of radiation dose irrespective of the dose protraction. Thus, potentially, these risk projection could underestimate cancer risks by 150-200%. Recently published studies reporting significantly increased risks of leukemia after multiple CT scans in children have raised concerns because of the absence of individual dosimetry and the possibility of confounding by indication or reverse causation. The risks in adults and the risks of lung and breast cancer, the most frequent cancers in the U.S. population, remain undetermined. To provide clarity and to address important gaps in our knowledge, we propose to extend the mortality follow-up of the 63,707 CFCS patients exposed to repeated diagnostic imaging fluoroscopies in 1930-1952 by additional 30 years (for a total of 68 years, 1950-2017) as well as to conduct for the first time incidence follow-up (1969-2017). We will use CFCS's large size, the long follow-up, the individual dose assessments and the similarities in radiation exposures between fluoroscopies and CT scans to gain an unprecedented opportunity to conduct a life course examination of radiation risks. To achieve CFCS aims, we will develop a new Fluoroscopy X-rays Organ- Specific (FLUXOR) Dosimetry System and link the cohort to the Canadian Mortality and Incidence Databases covering the entire population of Canada. In addition to radiation doses to multiple organs, we will have unique data on modifiable risk factors, such as smoking, to evaluate multi-factorial etiology of cancer outcomes. Applicability of radiation risks estimated in the cohort to the U.S. general population will be further examined by pooling the CFCS data with the data from the Massachusetts Fluoroscopy Cohort Study (n=13,385). The efficient study design will provide important and previously unavailable scientific evidence on the lifespan risks of protracted radiation exposures. The research team includes experts in radiation epidemiology, biostatistics and dosimetry and is uniquely qualified to assess the appropriateness of current radiation safety standards for diagnostic imaging procedures, in particular for CT scans.